Mechanisms of Osteoclast Dysfunction in Human Osteopetrosis: Abnormal Osteoclastogenesis and Lack of Osteoclast-Specific Adhesion Structures
| Autor: | Silvia Migliaccio, A. Corsi, Giulio De Rossi, Cesare Bosman, Paolo Bianco, Anna Taranta, Metello Iacobini, Renata Boldrini, Anna Teti, Lidia De Felice, Silvia Bernardini, Matteo Luciani |
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| Rok vydání: | 1999 |
| Předmět: |
Calcitonin
Pathology medicine.medical_specialty Podosome Endocrinology Diabetes and Metabolism Acid Phosphatase Antigens Differentiation Myelomonocytic Fluorescent Antibody Technique Osteoclasts Receptor Macrophage Colony-Stimulating Factor Bone resorption Antigens CD Osteoclast Cell Adhesion medicine Humans Receptors Vitronectin Orthopedics and Sports Medicine Calcitonin receptor Child Cell adhesion Tartrate-resistant acid phosphatase biology Histocytochemistry Tartrate-Resistant Acid Phosphatase Osteopetrosis Receptors Calcitonin Alkaline Phosphatase medicine.disease Cell biology Isoenzymes Genes src Microscopy Electron medicine.anatomical_structure biology.protein Female Vitronectin |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0884-0431 |
| Popis: | Osteoclasts from a patient affected by osteopetrosis were examined in vivo and in vitro. Iliac crest biopsy revealed an osteosclerotic pattern, with prominent numbers of osteoclasts noted for hypernuclearity and incomplete adherence to the bone surface. A population comprising tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated and mononuclear cells, and alkaline phosphatase-positive stromal fibroblasts was obtained in vitro from bone marrow. Mononuclear TRAP-positive precursors spontaneously fused in culture to form giant osteoclast-like cells. These cells expressed the osteoclast marker MMP-9 and calcitonin receptor, and lacked the macrophage marker, Fc receptor. Expression and distribution of c-src, c-fms, and CD68, and response to steroid hormones relevant to osteoclast differentiation and function were apparently normal, whereas cell retraction in response to calcitonin was impaired. TRAP-positive multinucleated cells did not form osteoclast-specific adhesion structures (clear zone, podosomes, or actin rings). Bone resorption rate was severely reduced in vitro. Focal adhesions and stress fibers were observed en lieu of podosomes and actin rings. Adhesion structures contained low levels of immunoreactive vitronectin receptor, most of this integrin being retained in cytoplasmic vesicles. These data provide the first characterization of abnormal differentiation and function of human osteopetrotic osteoclast-like cells. |
| Databáze: | OpenAIRE |
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